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Breast Cancer in Metro Manila and Rizal Province, Philippines

COMMENTARY

Epidemiology and Clinicopathology of Breast Cancer in Metro


Manila and Rizal Province, Philippines
Adriano Laudico1,2,3*, Maria Theresa M Redaniel4, Maria Rica Mirasol-
Lumague2,3, Cynthia A Mapua5, Gemma B Uy1, Eero Pukkala6 , Paola Pisani7
Abstract
The breast cancer incidence in the Philippines is among the highest in Asia. Age-standardized incidence
rates (ASR) in Metro Manila and Rizal Province derived from the Philippine Cancer Society-Manila Cancer
Registry and the Department of Health-Rizal Cancer Registry showed increase from 1980 to 2002, and were
significantly higher in 7 cities in Metro Manila and significantly lower in 14 cities/municipalities mostly in Rizal
Province. The AJCC Clinical Stage did not change from 1993 to 2002 among incident cases, the average
distribution being: I=5%, IIA=20%, IIB= 18%, IIIA=9%, IIIB=10%, IV=11%, Unknown=28%. The
International Agency for Research on Cancer attempted to run a randomized screening trial in 1995-1997 in the
Philippines based on clinical breast examination by trained nurses and midwives. Unfortunately, even after
home visits by a team equipped to perform needle biopsy, only 35% of screen-positive cases eventually had a
diagnostic test. The estimated prevalence of BRCA mutations among unselected patients in the Philippine General
Hospital (PGH) in 1998 was 5.1%, with a prevalence of 4.1% for BRCA2 mutations alone. There is a continuing
effort at improving IHC hormone receptor testing at PGH, particularly on early fixation in buffered formalin.
It was observed that hormone receptor-positive proportions tended to be higher in core needle biopsy specimens
(72%) compared to mastectomy specimens (65%). During the years 1991, 1994 and 1997, 97% of incident cases
of early breast cancer underwent modified radical mastectomy, 18% had postoperative radiotherapy, 51% had
adjuvant hormone treatment and 47% received adjuvant chemotherapy. Survival of incident cases in 1993 to
2002 was compared to that of Filipino-Americans and Caucasians in the SEER 13 database. The age-adjusted 5-
year relative survival, using period analysis, of Metro Manila residents, Filipino-Americans and Caucasians
were 58.6%, 89.6% and 88.3% respectively.
Key Words: Breast cancer - incidence trends - treatment - epidemiology - Philippines

Asian Pacific J Cancer Prev, 10, 167-172

Introduction many developing countries. This review was conducted


to assess the available epidemiologic and clinicopathologic
International agencies are in agreement that the global information on breast cancer in a developing country, the
cancer burden will continue to increase, and that the Philippines.
greater proportion of the increase will occur in developing
countries. Breast cancer has been for decades the most Incidence and Incidence Trends
common cancer among women in developed countries
and is now also the leading female cancer in most Two population-based cancer registries, the
developing countries (Curado et al., 2007). The incidence Department of Health – Rizal Cancer Registry (DOH-
is expected to increase, mainly due to decreasing fertility RCR) and the Philippine Cancer Society – Manila Cancer
and “westernization” of lifestyles. Registry (PCS-MCR), have been generating incidence data
An increase in breast cancer survival had been observed since the 1980s, and had contributed to the Cancer
in some developed nations, and was mainly attributed to Incidence in Five Continents (CIFC) of the International
earlier detection and appropriate adjuvant treatment of Agency for Research on Cancer starting with Volume V
early breast cancer. This is unfortunately not the case in (CANCERMondial http://www-dep.iarc.fr/ ). The

1
Dept of Surgery, Philippine General Hospital, University of the Philippines, Manila, 2Philippine Cancer Society-Manila Cancer
Registry, 3Dept of Health-Rizal Cancer Registry, Rizal, Philippines, 4Division of Clinical Epidemiology and Aging Research, German
Cancer Research Center, Heidelberg, Germany 5Bioinformatics Dept, Research and Biotechnology Division, St. Luke’s Medical
Center, camapua@yahoo.com, 6Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki,
Finland 7Cancer Epidemiology Unit, Dept of Biomedical Sciences and Human Oncology, University of Turin, Italy * For
correspondence: yago_md@yahoo.com, gemmauymd@yahoo.com

Asian Pacific Journal of Cancer Prevention, Vol 10, 2009 167


Adriano Laudico et al

Table 1. Numbers of Breast Cancer Cases and


Controls, Odds Ratios and 95% Confidence Limits by
Numbers of Full-term Pregnancies. From the nested case-
control study of the IARC trial on clinical breast examination
screening in Metro Manila and Rizal Province, Philippines,
2000-2001, OR estimates by uncontrolled logistic regression
(Parkin et al., 2002)
Pregnancies No. Cases No. Controls OR 95% CI
Nulliparous 25 115 3.3 1.6-6.7
1-2 30 161 2.7 1.4-5.4
3 16 161 1.3 0.7-3.1
4-5 23 244 1.3 0.6-2.6
≥6 14 193 1.0
Unknown 15 104 2.2 0.9-5.0

some adjoining cities (Laudico et al., 2008). Figure 3


Figure 1. Age-adjusted (World) Incidence Rates of illustrates the wide variance in 1998-2002 ASRs, with the
Female Breast Cancer per 100,000 in Asian Cancer cities of Manila, Quezon, San Juan, Mandaluyong, Makati,
Registries, U.S.A. Filipino and Non-Hispanic White Pasig and Parañaque having significantly higher ASRs.
Women in Los Angeles, and in Finland (Curado et al, The rates decrease eastward, with significantly lower rates
2007). seen in the rural areas of Rizal province (Redaniel et al.,
2008).
registries cover an area of 1,978 square kilometers with a Two factors may partially explain the variance – parity
population of 11.2 million (2000 Census). The area and internal migration. Many reports had consistently
includes the city of Manila, the historic and current capital demonstrated that decreasing parity increases breast
city, and surrounding highly urbanized and rapidly cancer risk, and vice versa. Table 1 shows that the nested
urbanizing cities and municipalities which are now case-control study in the International Agency for
collectively known as Metro Manila, also called the Research on Cancer (IARC) trial on clinical breast
National Capital Region (NCR). To the east are the rural examination screening in Metro Manila and Rizal
municipalities of Rizal Province. During the period 1998- Province (2000-2001) revealed an Odds Ratio (OR) of
2002, the overall age-standardized rate (ASR) was 52.2 3.3 (95% CI 1.6-6.7) among nulliparous women compared
(PCS-MCR 56.1, DOH-RCR 48.8) (Redaniel et al., 2008). to an OR of 1 among women with 6 or more full-term
Figure 1 shows that the Philippine ASR was lower than pregnancies (Parkin et al., 2002). The city of Manila had
the chosen American, Finnish and Israeli populations, but been home to the country’s elite and middle class since
higher than many other Asian populations. The ASR of the Spanish Colonial era. Manila was devastated during
Filipino-American residents in Los Angeles, U.S.A. was World War II, and the 1950s saw the beginning of massive
much higher than that of Filipinos residing in the real estate developments in the “suburbs”, in the form of
Philippines (Curado et al.,2007). gated subdivisions and other forms of housing for the
Figure 2 shows that temporal-spatial maps reveal that wealthy and middle class families. This started in Makati
the 1980-1984 ASRs had increased to those of 1998-2002, and Quezon City, followed by those in Mandaluyong, San
with the greatest increases seen in the city of Manila and Juan, Pasig and Parañaque. This massive housing

1980-1984 1998-2002
Figure 2. Age-adjusted (World) Incidence of Female Breast Cancer per 100,000 Person- years in Metro Manila
and Rizal Province, by Period (Laudico et al, 2008)

168 Asian Pacific Journal of Cancer Prevention, Vol 10, 2009


Breast Cancer in Metro Manila and Rizal Province, Philippines

Table 2. Distribution of 1,615 Incident Breast Cancer Patients by the American Joint Commission on Cancer
(AJCC) Stage and Diagnosis Year, Metro Manila, Philippines, N (%)
Stage (AJCC) 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 Total
I 6 (4.1) 9 (5.7) 7 (4.2) 8 (4.8) 8 (5.4) 6 (3.3) 13 (9.9) 11 (6.1) 6 (3.4) 8 (5.0) 82
IIA 19 (13.0) 26 (16.6) 23 (13.9) 35 (21.1) 30 (20.1) 36 (19.7) 29 (22.1) 45 (24.9) 46 (25.8) 29 (18.2) 318
IIB 29 (19.9) 23 (14.7) 25 (15.2) 23 (13.9) 21 (14.1) 36 (19.7) 22 (16.8) 27 (14.9) 33 (18.5) 44 (27.7) 283
IIIA 11 (7.5) 13 (8.3) 13 (7.9) 14 (8.4) 9 (6.0) 17 (9.3) 18 (13.7) 12 (6.6) 23 (12.9) 13 (8.2) 143
IIIB 16 (11.0) 15 (9.6) 13 (7.9) 20 (12.1) 16 (10.8) 20 (10.9) 9 (6.9) 14 (7.7) 23 (12.9) 10 (6.3) 156
IV 14 (9.6) 17 (10.8) 17 (10.3) 21 (12.7) 17 (11.4) 26 (14.2) 14 (10.7) 22 (12.2) 23 (12.9) 13 (8.2) 184
Unknown 51 (34.9) 54 (34.4) 67 (40.6) 45 (27.1) 48 (32.2) 42 (23.0) 26 (19.9) 50 (27.6) 24 (13.5) 42 (26.4) 449
Total 146 157 165 166 149 183 131 181 178 159 1,615

development did not occur in Caloocan, Malabon, equipped to perform needle biopsies, were formed, but
Navotas, Pasay, Las Piñas and Pateros. Although income- 42% of visited screen positive women actively refused
city-specific fertility rates over time may not be available, needle biopsy. Only 1,220 women (35%) eventually had
it is surmised that fertility rates in the high incidence areas a diagnostic test.
had decreased with increasing prosperity, relative to the The unexpected result that jeopardized the whole
lower incidence areas. Lifestyle changes are also usually intervention was the unforeseen reticence of women found
more substantial and rapid among the more affluent. This to have abnormalities and informed of the implications
housing boom and resulting migration of wealthy and to their life, to pursue diagnosis and treatment. The authors
middles class families has continued, and now involves also suggested that lack of trust in the health system and
the cities of Marikina, Cainta, Taguig, Las Piñas amd in one’s chances to be cured may discourage action. (Pisani
Muntinlupa, and an increase in breast cancer incidence et al., 2006). It is thus not unexpected that the stage
can be expected in the future. distributions of breast cancer have not changed
significantly during 1993-2002 (Table 2). The proportion
Screening and Clinical Stage of Stage I cases in 1993 was 4.11%, and 5.03% in 2002.
As a comparison, among Filipino residents in the United
The IARC attempted a population-based randomized States in 1992-1997, 36.3% and 47.8% were diagnosed
screening trial (1995-1997), using Clinical Breast in Stage I and Stage II respectively (Chu et al., 2002)
Examination (CBE) by trained nurses and midwives,
involving 12 municipalities (202 health centers), and
BRCA1 and BRCA2 Mutations
randomized by municipalities. Out of 151,168 women
interviewed and offered CBE, 3,479 were found to have The estimated prevalence of BRCA mutations among
lumps (screen positive) and were referred to identified unselected cases in the Philippine General Hospital in
outpatient clinics. Only 21% spontaneously complied. 1998 was 5.1% (95% CI: 2.6-7.6%), with a prevalence of
Home-visit teams, composed of a doctor and nurse 4.1% (95% CI: 1.8-6.4%) for BRCA2 mutations alone.
Compared with non-carrier cases, the cumulative risk of
breast cancer for first-degree relatives of mutation carriers
was 24.3% to age 50, compared with <4% for first-degree
relatives of non-carriers (RR = 6.6; 95% CI: 2.6-17.2).
(Matsuda et al., 2002)

Hormone Receptor Assay


Some current evidence-based clinical practice
guidelines suggest that hormonal receptor status (estrogen/
progesterone) should be the starting point for the systemic
treatment of breast cancer, be it in an adjuvant or metastatic
setting (NCCN 2008, Laudico et al., 2006). The
consequences of mislabeling a patient as hormone receptor
negative (HR-) could be dire, as this would deprive the
patient of appropriate treatment and could also lead to
treatment that may not be as effective as hormonal therapy.
Some reports notwithstanding, the authors believe that
Figure 3. Age-adjusted (World) Incidence of Female there ought to be no major differences in the proportions
Breast Cancer per 100,000 Person- years in Metro of hormone receptor positive cases (HR+) between most
Manila and Rizal Province for 1998-2002 (Laudico et ethnic groups, if standardization of procedures and scoring
al, 2008) methods were followed. A EUROCARE-based
Asian Pacific Journal of Cancer Prevention, Vol 10, 2009 169
Adriano Laudico et al in earlier stages among the SEER populations, as
publication reported that 83% of cases in European compared to Metro Manila residents. This further
countries were HR+ (Allemani et al., 2004). A SEER- highlights the difficulties in breast cancer screening and
based report showed that during 1992-1998, HR+ rates early detection in the Philippines.
among women 50 years of age and older ranged from
64% among Koreans to 84% among Non-Hispanic whites, Future Considerations
and was 79% among Filipinos (Li et al., 2002). Another
SEER-based report showed that in 1992-1997 and among It could be that the Philippine Department of Health
all women with breast cancer, the HR+ rate among (DoH) may now be interested in providing more support
Filipinos was 77% (Chu et al., 2001). to population-based cancer registration through additional
At the Philippine General Hospital, HR+ cases manpower to the two registries, Department Orders that
increased from 59% to 69% (p=0.003) after key breast would facilitate active cancer registration, and the
tissue specimen fixation procedures were implemented, promotion of a coordinated and standardized system. Two
including prompt fixation in buffered formalin and optimal existing registries are of interest, one in Cebu City in the
(10-36 hours) fixation (Uy et al, 2007). It was also noticed Central Philippines and the other in Davao City in
that the HR+ rates tended (p=0.5) to be higher in core Southern Philippines. These two cities are the second and
needle biopsy (CNB) specimens (71.9%) compared to third largest urban areas.
mastectomy specimens (64.5%). Factors that could explain From the data gathered for this review it seems obvious
these differences could be related to the highly labile that the strategy and methods of the Philippine Cancer
nature of the receptor proteins and the ability to promptly Control Program have not resulted in improvement in early
fix them in buffered formalin which could be inherently detection, and it would be appropriate to rethink and
different between CNB and mastectomy. refocus the Program. A modern and sustained campaign
Currently, we are unaware of any other publications to promote the message that breast cancer is curable ought
or reports from other Philippine hospitals regarding their to be a priority, while simultaneously improving the
experience on hormone receptor assay. Initiatives by availability of and accessibility to basic diagnostic and
individual physicians in the past to try to improve the treatment facilities in public hospitals. The number of
quality of assays have been unsuccessful. The Philippine medically needy patients is expected to increase and it
College of Surgeons had just initiated a national effort at would be futile to launch a new and correct public
improving and standardizing immunohistochemical (IHC) information campaign if a large segment of the population
testing of hormone receptors. cannot afford the expense.
There is already enough indirect evidence that clinical
Adjuvant Treatment breast examination and breast self-examination can
increase survival, and future intervention studies should
In spite of, or perhaps because of, the persistent see if a combination of an appropriate message that is
anecdotal complaints of Philippine surgeons nationwide adequately delivered, in combination with sufficient public
that in their setting most hormone receptor assay results funding of necessary services for the needy, could work.
were “negative”, adjuvant hormone therapy (HT) was The Philippine College of Surgeons (PCS) needs to
given to 51% of cases. Out of 738 incident cases of early step up efforts at improving compliance with its Clinical
breast cancer in 1991, 1994 and 1997, 97% underwent Practice Guidelines, which are truly evidence-based and
modified radical mastectomy, only 18% had postoperative community-oriented. This it could do through its chapter
radiotherapy, and 47% received chemotherapy (CT). The members, relating with like-minded health organizations,
use of adjuvant HT significantly increased over time in and insurance companies and HMOs. The PCS can start
all age-groups. Among the 524 patients who received by sustaining the effort at educating surgeons to properly
systemic adjuvant treatment, 38.0% had a combination fix CNB specimens, and identifying and promoting
of HT and CT. The proportions of women receiving regional laboratories that can accurately perform hormone
combined CT and HT also increased over time. Majority receptor assays.
of the prescribing physicians were either surgeons (68.9%)
or medical oncologists (29.2%), and the proportions did References
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